TDF for 3 Years Reduces Fibrosis Progression in Patients With CHB, HBV DNA > 2000 IU/mL, and Minimally Elevated ALT
Source: 2018 Annual Meeting of the American Association for the Study of Liver Diseases*
Released: November 20, 2018
Multicenter, randomized, triple-blind, placebo-controlled phase IV trial[1,2]
Summary of Key Conclusions
In patients with chronic HBV infection (CHB), HBV DNA > 2000 IU/mL, and minimally elevated ALT at 1-2 x upper limit of normal (ULN), 3 years of tenofovir disoproxil fumarate (TDF) significantly decreased risk of fibrosis progression vs placebo
Fibrosis progression: TDF, 23.1%; placebo, 44.8%
Relative risk (RR) for any increase in Ishak fibrosis: 0.52 (95% CI: 0.31-0.85; P = .01)
TDF associated with significantly lower risk of cirrhosis at Year 3
RR for cirrhosis (Ishak stage 5/6): 0.23 (95% CI: 0.06-0.88; P = .05)
Comparable rates of decrease in inflammatory score between arms (P = .38)
Improved inflammatory score: TDF, n = 34 (52.3%); placebo, n = 29 (43.3%)
1 patient receiving TDF experienced > 30% decrease in estimated glomerular filtration rate (eGFR)
Background
HBV guidelines from American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL) recommend HBV therapy for patients with CHB based on HBV DNA levels (differing by hepatitis B e antigen [HBeAg] status for AASLD and APASL), ALT levels, and/or liver biopsy results[3-5]
AASLD
HBeAg positive: treat if HBV DNA > 20,000 IU/mL or ALT ≥ 2 x ULN
HBeAg negative: treat if HBV DNA ≥ 2000 IU/mL or ALT ≥ 2 x ULN
EASL, HBeAg positive or negative
Treat if HBV DNA > 20,000 IU/mL or ALT > 2 x ULN
Treat if HBV DNA > 2000 IU/mL and (ALT > ULN and/or moderate necroinflammation/fibrosis)
APASL
HBeAg positive: treat if HBV DNA > 20,000 IU/mL or ALT > 2 x ULN
HBeAg negative: treat if HBV DNA > 2000 IU/mL or ALT > 2 x ULN
Utility of HBV therapy not established in patients with minimally raised ALT > ULN but < 2 x ULN[3]
Current study compared efficacy and safety of TDF vs placebo to prevent disease progression in patients with CHB, HBV DNA > 2000 IU/mL, and ALT 1-2 x ULN[1] 作者: StephenW 时间: 2018-11-30 04:58
TDF 3年可减少CHB患者的纤维化进展，HBV DNA> 2000 IU / mL，ALT升高最低
资料来源：2018年美国肝病研究协会年会*
发布日期：2018年11月20日
多中心，随机，三盲，安慰剂对照的IV期试验[1,2]
主要结论摘要
在慢性HBV感染（CHB）患者中，HBV DNA> 2000 IU / mL，ALT在1-2 x正常上限（ULN）的最低升高，3年的替诺福韦地索普西富马酸盐（TDF）显着降低纤维化进展的风险与安慰剂
纤维化进展：TDF，23.1％;安慰剂，44.8％
Ishak纤维化增加的相对风险（RR）：0.52（95％CI：0.31-0.85; P = .01）
TDF与3年级肝硬化风险显着降低有关
肝硬化的RR（Ishak分期5/6）：0.23（95％CI：0.06-0.88; P = .05）
两组间炎症评分降低的可比率（P = .38）
改善炎症评分：TDF，n = 34（52.3％）;安慰剂，n = 29（43.3％）
1名接受TDF治疗的患者肾小球滤过率（eGFR）下降> 30％
背景
美国肝病研究协会（AASLD），欧洲肝脏研究协会（EASL）和亚太肝脏研究协会（APASL）的HBV指南建议HBV治疗基于HBV的CHB患者DNA水平（不同于AASLD和APASL的乙型肝炎e抗原[HBeAg]状态），ALT水平和/或肝脏活检结果[3-5]
AASLD
HBeAg阳性：治疗HBV DNA> 20,000 IU / mL或ALT≥2x ULN
HBeAg阴性：治疗HBV DNA是否≥2000IU/ mL或ALT≥2×ULN
EASL，HBeAg阳性或阴性
治疗HBV DNA> 20,000 IU / mL或ALT> 2 x ULN
治疗HBV DNA> 2000 IU / mL和（ALT> ULN和/或中度坏死性炎症/纤维化）
APASL
HBeAg阳性：治疗HBV DNA> 20,000 IU / mL或ALT> 2 x ULN
HBeAg阴性：治疗HBV DNA> 2000 IU / mL或ALT> 2 x ULN
在ALT> ULN但<2 x ULN [3]的最低升高患者中未建立HBV治疗的效用
目前的研究比较了TDF与安慰剂的疗效和安全性，以预防CHB，HBV DNA> 2000 IU / mL和ALT 1-2 x ULN患者的疾病进展[1]作者: StephenW 时间: 2018-11-30 04:58